Sepsis: Never Ending Story

19. July 2016
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Following a septicaemia event, patients have for months or even years later an increased risk of death. A research team has now discovered that this not only derives from pre-existing conditions, but is also a direct result of blood poisoning.

Many patients die in the first few months or years following a blood poisoning (sepsis) – long after the acute infection has subsided. The risk of death as such, according to a study from the 1990s, was heightened for up to five years after the septicaemia. Until now it has been unclear whether this is a direct result of sepsis – or whether the patients simply have more pre-existing conditions that contribute to their early death. This is because with pre-existing conditions the risk of developing blood poisoning is elevated.

Now a research team led by Hallie Prescott of the Department of Pulmonary and Critical Care Medicine at the University of Michigan in Ann Arbor (USA) studied the causes of the increased mortality risk for the first time in great detail. The researchers published their results in the specialist journal BMJ.

Blood poisoning is a serious complication stemming from what is initially a locally limited inflammation. In order to fight the infection, the body releases large amounts of messenger substances into the bloodstream. These lead to pronounced symptoms such as swelling, circulatory disorders, a sharp drop in blood pressure and, in serious cases, to organ failure.

Comparison with the most similar patient groups

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Hallie Prescott © University of Michigan Health System

Scientists led by Prescott analysed questionnaires and medical records of more than 37,000 patients who are participating in or participated in the “University of Michigan’s Health and Retirement Study“(HRS) – an ongoing longitudinal study involving older Americans. “We know that sicker patients have a higher risk of blood poisoning”, says Prescott. “Therefore, we wondered whether pre-existing conditions influence the risk of subsequent death after a sepsis”.

To this extent Prescott and her team analysed the risk of death of 960 patients during the period of 31 days to two years after having been admitted for sepsis treatment in a hospital. They compared this data with the risk of death for three other groups which were similar to the sepsis patients in as many aspects as possible: for example in age, gender, ethnicity, current health history. Patients therein included were aged 65 years or older.

The three comparison groups included 777 patients who had not been in hospital since the last enquiry in the HRS study, 788 patients who were treated in the hospital for an infection involving no sepsis, and 504 patients who were treated for acute sterile inflammation. This type of inflammation is not caused by pathogens, but rather by tissue damage – these include injury, burns and heart attacks.

By looking at these groups, the researchers were able to draw conclusions about the risk of death by sepsis compared to healthy patients, to patients with infection without pronounced inflammatory reaction, and to patients with singular inflammation events not involving bacterial infection.

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Characteristics of the different patient groups © Hallie Prescott, University of Michigan Health system

Risk of death following sepsis is high

Of the sepsis patients who had survived the first 30 days after hospital admission, about 40 percent died in the following two years. Blood poisoning here, compared to patients who were not hospitalised, was linked to a 22 percent increased risk of death. This risk remained elevated over the entire two year period. Compared to patients with a simple infection, the risk of death by sepsis was higher by 10 percent, compared to patients with a sterile inflammation by 16 percent.

“This is in our view a very surprising and interesting result. It means that subsequent death by sepsis cannot be explained adequately by the patient’s age, sociodemographic characteristics or health prior to blood poisoning”, Prescott says. “It also means at the same time that increased mortality is more distinctly accessible to treatment measures than previously thought”.

However, the study is just the beginning in understanding the causes and contexts of the high death rate more accurately, the researchers point out. Since their study was purely observational, one cannot say with certainty whether the blood poisoning is really the cause of the increased mortality. “Therefore, it is now very important to understand the biological processes that contribute to the increased mortality rate of sepsis”, Prescott says. “On this basis, one can potentially develop new treatments”.

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Survival rate of patients following sepsis (red) compared to healthy individuals (top), patients with simple infection (centre) and patients with sterile inflammation. © Hallie Prescott, University of Michigan Health System

Biological mechanisms as a starting point for new treatments

Previous studies suggest that a blood infection leads to biological changes that could lead to increased mortality rates. This is shown by mice after an experimentally induced sepsis as an increase in tumours and an accelerated progression of atherosclerosis. Moreover they often die from infections caused by bacteria or fungi.

Even in studies of people who have survived a sepsis event, high rates of infection, cancer and deaths due to cardiovascular diseases were observed. Another study suggests that epigenetic mechanisms are an important factor after recovery from sepsis – a factor which contributes to permanently suppressed immune function and the development of atherosclerosis.

In Prescott’s study as well, patients frequently died on account of infection during the months and years after the septicaemia. This implies that the increased risk of infection and permanently impaired immune function might be able to be used as targets for treatment measures, the authors write.

“We now urgently need more research in order to develop better treatment approaches which can increase the life expectancy of patients following sepsis and improve their quality of life”, says Prescott. Furthermore, the results suggest that patients should be monitored more closely after recovering from sepsis, in order to detect any deterioration in their health at an early stage.

At the same time they could serve as a basis for informing patients and their families about life after of blood poisoning – so that they pay particular attention to the patient’s health, but also to enable them to prepare for a possible early death.

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